Helen Torley, Halozyme's President and Chief Executive Officer, who will provide an update on our business, and Darren Snellgrove, our Chief Financial Officer, will review our financial results as well as our outlook. Certain non-GAAP or adjusted financial measures are reconciled with the comparable GAAP financial measures in our earnings press release and slide presentation. I am pleased to report our results from an exceptionally strong second quarter, led by ENHANZE royalty revenue growth and new deal momentum that resulted in meaningful upfront milestones. I will start with the broadening diversification and record growth of our royalty revenue streams.
We are reporting increasing contributions of our newer launch products, Opdivo SC, Ocrevus SC, and RYBREVANT SC, to our royalty revenues with 80% growth quarter-on-quarter. This is repeating and building on top of the success and continued growth and performance of DARZALEX SC, VYVGART Hytrulo, and PHESGO. This is exactly what I meant by the compounding platform engine, multiple winners creating revenue diversification and durability. The new CLAs contributed $35.5 million in upfront collaboration revenue in the quarter, approximately evenly split across ENHANZE and Hypercon.
This was also an important contributor to record total revenue in the quarter. In the second quarter, we advanced our pipeline of future potential royalty streams with two new phase I study starts. For the second quarter, total revenue increased 48% year-over-year to $481 million. This was largely driven by robust royalty revenues of $308 million, a strong 50% year-over-year growth.